"Simple blood test could soon diagnose if patient has cancer and how advanced it is," reports the Mail Online. But this is a rather premature headline given the early stage of the research that the news is based on...

"Simple blood test could soon diagnose if patient has cancer and how advanced it is," reports the Mail Online. But this is a rather premature headline given the early stage of the research that the news is based on.

The blood of people with cancer contains DNA from the tumour, which may enter the blood after some of the tumour cells naturally die. However, blood also contains DNA from normal non-cancerous cells.

Researchers developed a technique called CAPP-Seq (cancer personalised profiling by deep sequencing) to detect the small amounts of tumour DNA in the blood of people with non-small-cell lung cancer. They identified parts of the DNA frequently mutated in non-small-cell lung cancer and developed a filter to "enrich" them. These were sequenced thousands of times to identify the mutations.

Why this research could be important

It is possible to treat non-small-cell lung cancer with surgery (in conjunction with chemotherapy) if you are healthy and the cancer is confined to one lung.

Being able to monitor the size and spread of the tumour using blood tests could – in the future – be a way to help patients and their medical team decide on the best course of treatment.

The researchers were able to detect circulating tumour DNA in 50% of people with early-stage cancers and in all people with later-stage cancers. Levels of circulating tumour DNA were also found to correlate with tumour size and response to treatment.

This is a promising technique that could potentially have a role one day in monitoring cancer progression and response to treatment, and possibly even in screening and diagnosis.

However, it has only been tested on a small number of people. Further studies will be needed to see the best ways to use it and how well it works for other cancers.

Where did the story come from?

The study was carried out by researchers from Stanford University and was funded by the US Department of Defense, the National Institutes of Health Director's New Innovator Award Program, the Ludwig Institute for Cancer Research, the Radiological Society of North America, the Association of American Cancer Institutes' Translational Cancer Research Fellowship, the Siebel Stem Cell Institute, the Thomas and Stacey Siebel Foundation, and Doris Duke Clinical Scientist Development Awards.

The Mail Online's coverage was a little optimistic. They report that, "According to the medics, the new test works for the most common types of cancer, including breast, lung and prostate. It could even be used to screen healthy or at-risk patients for signs of the illness."

Although this is ultimately what the researchers want to achieve, so far they have only used the technique to detect tumour DNA in the blood of a small sample of people with non-small-cell lung cancer, but it could be modified to detect other cancers in theory.

In addition, although the technique was good at detecting stage II to IV tumours, it was less good at detecting stage I cancers. The researchers state that methodological improvements are required to detect these early-stage cancers.

More research in larger populations is needed before it is known whether any test could be used either for monitoring the response to treatment in people with cancer, or possibly even for detecting cancer.

What kind of research was this?

The blood of people with cancer contains DNA from the tumour cells. How tumour DNA reaches the blood is unclear, but it may be released as the tumour cells die naturally. However, blood also contains DNA from normal, non-cancerous cells.

This was a laboratory-based study that aimed to develop a technique to detect and analyse circulating tumour DNA in blood.

This technique would be particularly useful for monitoring tumours and could have the potential to be involved in the screening or diagnosis of tumours.

What did the research involve?

The researchers were initially interested in optimising the technique for the most common type of lung cancer (non-small-cell), although they point out that theoretically it could be used for any cancer.

The researchers initially designed a "selector", or filter. This was a series of DNA "probes" that corresponded to regions of DNA that are often mutated in non-small-cell lung cancer. The researchers chose the regions based on mutations found in people with non-small-cell lung cancer in national databases such as the Cancer Genome Atlas.

In total, the selector targeted 521 regions of DNA that code for protein (exons) and 13 intervening regions (introns) in 139 genes, corresponding to 0.004% of the human genome. These DNA probes were used to select the DNA regions to be sequenced.

The researchers performed what is known as "deep" sequencing, meaning that these specific regions were sequenced multiple times (about 10,000 times). This was to detect any mutations that may be present.

They initially used the selector and deep sequencing – together known as cancer personalised profiling – by deep sequencing (CAPP-Seq) to detect mutations in tumour samples from 17 people with non-small-cell lung cancer.

They then assessed how accurate CAPP-Seq was for monitoring disease and detecting minimal residual disease using blood samples from five healthy people and 35 samples collected from 13 people with non-small-cell lung cancer.

The researchers also determined whether the amount of circulating tumour DNA in blood corresponded to tumour burden and whether the technique could potentially be used for tumour screening.

What were the basic results?

Detection

When CAPP-Seq was applied to tumour samples from 17 people with non-small-cell lung cancer, it detected all the mutations that were known to be present from previous diagnostic work. It also detected additional mutations.

CAPP-Seq was then used to detect and analyse circulating tumour DNA in the blood. Circulating tumour DNA was detected in all people with stage II to IV non-small-cell lung cancer and 50% of people with stage I cancer.

Monitoring

The researchers then analysed whether the levels of circulating tumour DNA in the blood correlated with tumour volumes. They found that levels of circulating tumour DNA in the blood increased as tumour volume increased (measured using computerised tomography and positron emission tomography).

They then monitored levels of circulating tumour DNA in the blood of people who were undergoing cancer treatment. Again, levels of circulating tumour DNA in the blood correlated with tumour volumes.

From the results in two people with stage II or III disease, it seems that this technique may have potential in identifying people with residual disease after therapy. This is because one person was thought to have been successfully treated, but CAPP-Seq detected low levels of circulating tumour DNA. This person experienced disease recurrence and ultimately died.

Two people with early-stage disease were also monitored after treatment. One of these people had a mass thought to represent residual disease after treatment. However, CAPP-Seq detected no circulating tumour DNA and the person remained disease-free for the duration of the study.

Screening

The researchers also assessed the potential for using CAPP-Seq as a screening tool by testing blood samples from all the people in their cohort. The technique could detect all the people with cancer with circulating tumour DNA levels above a certain level (0.4% of all circulating DNA). It was also able to detect specific mutations in some patients.

How did the researchers interpret the results?

The researchers conclude that CAPP-Seq allows for "highly sensitive and non-invasive detection of [circulating tumour DNA] in the vast majority of patients with [non-small-cell lung cancer] at low cost. CAPP-Seq could therefore be routinely applied clinically and had the potential for accelerating the personalised detection, therapy and monitoring of cancer.

"We anticipate that CAPP-Seq will prove valuable in a variety of clinical settings, including in assessment of cancer DNA in alternative biological fluids and specimens with low cancer cell content," they said.

Conclusion

In this study, researchers have developed a technique called CAPP-Seq to detect and analyse the small amounts of tumour DNA in the blood. The researchers tested the technique on samples from five healthy people and 35 samples collected from 13 people with non-small-cell lung cancer.

Circulating tumour DNA was detected in 50% of people with stage I cancer (a small cancer in one area of the lung) and in all people with stage II to IV non-small-cell lung cancer (the three stages covering larger lung cancers – those that may have spread to the lymph nodes or spread to the rest of the body). Levels of circulating tumour DNA were also found to correlate with tumour size and response to treatment.

Overall, this is promising research into a technique that could potentially have a role in one day monitoring cancer progression and response to treatment, and possibly even in screening and diagnosis.

However, further studies in more people will be required to determine how well the technique works both for non-small-cell cancer and for other cancers, and to see if and how it could be used in cancer diagnosis and treatment.